LCP-Tacro™ (Veloxis Pharmaceuticals) is an extended release once-daily (qd) tablet MeltDose® formulation of tacrolimus (TAC) that has shown enhanced pharmacokinetics, optimized dosing, and noninferior efficacy compared to TAC twice-daily (bid) capsules (Prograf®; AstellasPharma). This study evaluated the pharmacokinetics and safety of LCP-Tacro vs. Prograf.This phase II, three-sequence, open label, multicenter study included 60 adult recipients of a renal transplant at least six months prior to enrollment with serum creatinine ≤2 mg/dL and on stable oral Prograf therapy with TAC trough levels 7-12 ng/mL for at least two weeks. Patients were on Prograf bid for seven days. On day 8 each patient was converted to LCP-Tacro tablets using a dose conversion ratio ranging from 0.66 to 0.80 followed by 14 days on LCP-Tacro qd before converting back to standard Prograf and then followed for 30 days. Plasma levels of TAC were obtained two hours following dosing on days 7, 14, and 21.

Results on LCP-Tacro vs. Baseline Prograf

Parameter

Prograf (n=47) Day 7

LCP-Tacro (n=47) Day 14

LCP-Tacro (n=47) Day 21

Cmin (ng/mL), mean ± SD

7.0 ± 1.5

7.0 ± 2.3

6.9 ± 2.2

Cmax (ng/mL), range

8-49

6-25

7-38

Cmax (ng/mL), mean ± SD

19.1 ± 8.2*

13.5 ± 4.8*

13.9 ± 5.8*

Patients with Cmax> 20 ng/mL, n (%)

18 (38%)*

6 (13%)*

7 (15%)*

Degree of fluctuation (%), mean ± SD

127.4 ± 57.3*

73.2 ± 45.0*

77.0 ± 50.6*

Degree of swing (%), mean ± SD

174.6 ± 93.7*

102.8 ± 75.2*

110.1 ± 89.2*

Tmax (hr), median

1.82

6.0

6.0

Tmax (hr), minimum-maximum

0.5-24*

1.0-16.0*

1.5-16.0*

* = p<0.05

Cmax and the percent fluctuation and value swing were significantly lower when qd LCP-Tacro tablets were administered compared to bid therapy with Prograf, while Tmax was significantly higher. Despite comparable trough levels between LCP-Tacro and Prograf, a significant proportion of patients had very high Cmax and the proportion of patients with very high Cmax was notably lower with LCP-Tacro. The incidence, type and severity of AEs in this study were in the range expected for each treatment.Conclusion: Patients could be converted to LCP-Tacro at a mean conversion ratio of 0.71 and at a fixed dose that was approximately 30% less than the total daily dose of Prograf. LCP-Tacro reduces Cmax in the subset of patients with high Cmax as well as in the overall population.Keywords: Pharmacokinetics; Safety; Kidney transplantation; Dosage